In a study of more than 3000 long-term survivors of childhood cancer, whole genome sequencing revealed that 12% carried mutations associated with increased cancer risk.1

"While there is extensive scientific literature on the late effects of cancer therapy, including the risk that survivors will develop subsequent malignancies, until now little was known about the genetic contribution," said Jinghui Zhang, PhD, chair of the St. Jude Children's Research Hopsital Department of Computational Biology and co-senior investigator on the study, which was presented at the the 2017 American Association for Cancer Research Annual Meeting.

The researchers analyzed the whole genome information from 3007 survivors of childhood cancer for germline mutations in 156 genes associated with increased cancer risk, 60 of which are inherited in an autosomal dominant manner and require a mutation in only one copy of a gene to cause cancer predisposition. Twelve percent of survivors had a mutation in one of the 156 genes and approximately 6% had a mutation in 1 of the 60 cancer-predisposition genes.

The most commonly mutated genes were the breast cancer associated BRCA1 and BRAC2 genes. Breast cancer was the most frequently diagnosed second cancer with 60 cases of breast cancer in 53 participants and 26 survivors with mutations in at least 1 gene. RB1, NF1, and TP53 were other frequently mutated genes.

Based on these findings the researchers recommend expanding screening for childhood cancer survivors. "These results suggest that many more childhood cancer survivors would likely benefit from genetic screening and counseling," said Leslie Robison, PhD, chair of the St. Jude Department of Epidemiology and Cancer Control and co-senior investigator. "For cancer survivors, this research marks the beginning of a new era in cancer surveillance and prevention," said Dr Zhang. The researchers believe that these findings will be beneficial to the development of personalized therapeutic treatments based on genetic profiles for children with newly diagnosed cancer.